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Antihypertrophic actions of NO-independent soluble guanylyl cyclase (sGC) ligands BAY 41-2272 and BAY 58-2667 in vitro
BMC Pharmacology volume 9, Article number: P59 (2009)
Over the last decade, we have shown that cGMP, derived from bradykinin, nitric oxide (NO•, both from endogenous and exogenous sources) or natriuretic peptides, is a potent inhibitor of cardiac hypertrophy, across isolated cardiomyocytes and intact hearts both ex vivo and in vivo. However, NO• bioavailability is reduced due to scavenging by ROS; furthermore, oxidation of sGC may result in sGC dysfunction (including loss of responsiveness to NO•). In the present study, we tested the hypothesis that the NO•-independent sGC stimulator BAY 41-2272 and the NO-independent sGC activator BAY 58-2667 elicit powerful antihypertrophic actions.
Materials and methods
Neonatal rat cardiomyocytes were incubated at 37°C in the presence of the hypertrophic stimulus, endothelin-1 (ET1, 60 nM) ± BAY 41-2272 or BAY 58-2667 (0.01–0.3 μM) for 48 h in serum-free conditions. Cardiomyocyte hypertrophy was assessed in live cells using conventional in vitro markers of hypertrophy, two dimensional area and cardiomyocyte de novo protein synthesis. Results were expressed as % paired control cardiomyocytes, mean ± SE.
See Table 1.
These results provide evidence that BAY 41-2272 and BAY 58-2667 elicit concentration-dependent inhibition of cardiac hypertrophy in vitro, in the absence of confounding haemodynamic factors and even at low (submicromolar) concentrations. These novel NO•-independent sGC ligands thus potentially may serve as useful antihypertrophic agents in patients, independent of blood pressure.
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Ritchie, R., Irvine, J., Love, J. et al. Antihypertrophic actions of NO-independent soluble guanylyl cyclase (sGC) ligands BAY 41-2272 and BAY 58-2667 in vitro. BMC Pharmacol 9 (Suppl 1), P59 (2009). https://doi.org/10.1186/1471-2210-9-S1-P59
- Nitric Oxide
- Cardiac Hypertrophy
- Guanylyl Cyclase
- Cardiomyocyte Hypertrophy
- Soluble Guanylyl Cyclase